血清PEDF及PEDF基因启动子区多态性与2型糖尿病患者微量白蛋白尿的相关性

Association of serum pigment epithelium-derived factor and polymorphism in promoter region of pigment epithelium-derived factor gene with microalbuminuria in type 2 diabetes mellitus patients

目的 :探讨福建地区汉族2型糖尿病患者血清色素上皮衍生因子水平(pigment epithelium-derived factor,PEDF)及PEDF基因启动子区rs1294385单核苷酸多态性与微量白蛋白尿的关系。方法 :471例2型糖尿病患者根据尿白蛋白/肌酐比值(urinary albumin to creatinine ratio,UACR)分为正常组(UACR<30μg/mg,NAU组)246例、微量白蛋白尿组(30μg/mg≤UACR<300μg/mg,MAU组)225例,使用PCR-RFLP方法检测PEDF基因启动子区rs1294385的多态性,同时检测血清PEDF水平及空腹血糖、空腹胰岛素、糖化血红蛋白、血脂等指标。结果:MAU组的血清PEDF水平高于NAU组,差异有统计学意义(P<0.05);偏相关分析显示血清PEDF水平与UACR呈正相关(P<0.05);PEDF基因启动子区rs1294385的基因型(GG型、GA型和AA型)和等位基因(G/A)在NAU、MAU两组间的分布存在差异,且差异有统计学意义(P<0.05);GA基因型出现微量白蛋白尿的风险是GG基因型的1.838倍,GA+AA基因型出现微量白蛋白尿的风险是GG基因型的1.862倍,差异有统计学意义(P<0.05)。结论:2型糖尿病患者血清PEDF水平随微量白蛋白尿的出现而增高;福建地区汉族2型糖尿病患者PEDF基因启动子区rs1294385多态性与微量白蛋白尿明显相关,携带A等位基因可能增加2型糖尿病患者发生微量白蛋白尿的机率。

Objective：To investigate the relationship between serum pigment epithelium-derived factor（PEDF） level,PEDF gene polymorphism in promoter region rs1294385 and microalbuminuria in type 2 diabetes mellitus（T2DM）of Fujian Han population.Methods：According to urinary albumin to creatinine ratio（UACR）,471 T2 DM patients were divided into the normal albuminuria group（the NAU group,UACR30 μg / mg,n=246） and the microalbuminuria group（the MAU group,30 μg / mg≤UACR300 μg / mg,n =225）. The PEDF gene rs1294385 G →A polymorphism was measured based on polymerase chain reaction restriction fragment length polymorphism（PCR-RFLP）. Meanwhile,serum PEDF level,fasting plasma glucose（FPG）,fasting insulin（FINS）,glycosylated hemoglobin（Hb A1c） and blood lipid were measured. Results：The level of serum PEDF in the MAU group was significantly higher than that in the NAU group（P〈0.05）. According to partial correlation analysis,serum PEDF level was positively related with UACR（P〈0.05）. There were significant differences between the frequencies of PEDF gene rs1294385 G →A genotype（GG genotype,GA genotype and AA genotype）and allele（G / A）of the NAU group and those of the MAU group（P〈0.05）. The risk ratio of GA genotype carriers suffering microalbuminuria was 1.838 times higher than that of GG genotype,while the risk ratio of GA and AA genotype carriers suffering microalbuminuria was 1.862 times higher than that of GG genotype（P〈0.05）. Conclusion：Elevation of serum PEDF level is in accordance with the development of microalbuminuria in T2 DM patients. Gene polymorphism in promoter region rs1294385 G→A of PEDF gene is closely related with microalbuminuria in T2 DM patients of Fujian Han population. Moreover,T2 DM patients with carriers of the A allele gene may have a higher risk of suffering from microalbuminuria.